Hydrochloric Acid → 2-[2-(3-Chloro-benzyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N-dicyclohexyl-acetamide

HRID 1170693Notes

Reaction equation

HRID 1170693 reaction equation
C(O[C:6](=O)[NH:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=1[NH2:16])(C)(C)C.[CH:18]1([CH:24]=O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.Cl[C:27]1[CH:28]=[C:29]([CH2:33][C:34]([OH:36])=O)[CH:30]=[CH:31][CH:32]=1.[CH:37]1([N+:43]#[C-])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.[ClH:45]>CO.O1CCOCC1>[Cl:45][C:22]1[CH:23]=[C:18]([CH:19]=[CH:20][CH:21]=1)[CH2:24][C:6]1[N:7]([CH:33]([CH:29]2[CH2:28][CH2:27][CH2:32][CH2:31][CH2:30]2)[C:34]([NH:43][CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)=[O:36])[C:8]2[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=2[N:16]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 158793-Chlorophenylacetic acidHCID 16275CyclohexanecarboxaldehydeHCID 79129Cyclohexyl isocyanideHCID 66619231tert-Butyl (2-amino-4,5-difluorophenyl)carbamate

Product 1

HCID 673721412-[2-(3-Chloro-benzyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N-dicyclohexyl-acetamideYield 21%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester (36.64 mg, 0.15 mmol, 1.0 equiv) in methanol (2.0 mL) was added cyclohexanecarbaldehyde (25.80 mg, 27.08 μL, 0.23 mmol, 1.5 equiv; [2043-61-0]) and the mixture stirred at rt. After 30 min, (3-chloro-phenyl)-acetic acid (34.12 mg, 0.20 mmol, 1.33 equiv; [CAS RN 1878-65-5]) and cyclohexyl isocyanide (16.38 mg, 18.41 μL, 0.15 mmol, 1.0 equiv; [931-53-3]) were added and stirring continued at rt for 2 h. A solution of 4 M HCl in dioxane (0.2 mL) was added and the reaction mixture stirred at rt overnight. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 15.7 mg (21%) of the title compound. MS (ISP): 500.2 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at rt for 2 h
  3. stirringthe reaction mixture stirred at rt overnight
  4. customRemoval of the solvent mixture
  5. customunder reduced pressure and purification by preparative HPLC on reversed phase
  6. washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-64af66e21b8a46c6a3982d0a2022a8e1
Source dataset
uspto-grants-2010_11
Patent number
US07825258B2

Reaction notes

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